GeneBe

GALC

galactosylceramidase, the group of Glycoside hydrolases

Basic information

Region (hg38): 14:87837820-87993665

Links

ENSG00000054983 ∙ NCBI:2581 ∙ OMIM:606890 ∙ HGNC:4115 ∙ Uniprot:P54803 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Krabbe disease (Definitive), mode of inheritance: AR
  • Krabbe disease (Definitive), mode of inheritance: AR
  • Krabbe disease (Strong), mode of inheritance: AR
  • Krabbe disease (Strong), mode of inheritance: AR
  • Krabbe disease (Strong), mode of inheritance: AR
  • Krabbe disease (Definitive), mode of inheritance: AR
  • Krabbe disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Krabbe diseaseARBiochemicalBMT/HSCT have been described, and in presymptomatic infants as well as older mildly-affected individuals, this treatment may improve and preserve cognitive function (ie, presymptomatic transplant has much better neurological outcomes)Biochemical; Neurologic14024503; 3123790; 4773865; 1817026; 1817027; 2056315; 1891085; 8297359; 7581365; 9449482; 8940268; 9338580; 9545360; 10833326; 15901860; 16607461; 17579360; 19332366; 21070211; 20301416; 20886637; 22115770; 22704718; 23462331; 23276707; 33832819

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GALC gene.

  • Galactosylceramide_beta-galactosidase_deficiency (1206 variants)
  • not_provided (261 variants)
  • not_specified (68 variants)
  • Inborn_genetic_diseases (57 variants)
  • GALC-related_disorder (23 variants)
  • Intellectual_disability (6 variants)
  • See_cases (4 variants)
  • EEG_abnormality (2 variants)
  • Small_for_gestational_age (2 variants)
  • Progressive_visual_loss (2 variants)
  • Amblyopia (2 variants)
  • Seizure (2 variants)
  • Developmental_regression (2 variants)
  • EMG:_axonal_abnormality (2 variants)
  • Hemiparesis (2 variants)
  • Strabismus (2 variants)
  • Leukodystrophy (2 variants)
  • Fetal_growth_restriction (2 variants)
  • Global_developmental_delay (2 variants)
  • Dysmyelinating_leukodystrophy (2 variants)
  • Status_epilepticus (2 variants)
  • Nystagmus (2 variants)
  • Breech_presentation (2 variants)
  • Spastic_ataxia (2 variants)
  • Loss_of_ambulation (2 variants)
  • EMG_abnormality (2 variants)
  • Neonatal_hypoglycemia (2 variants)
  • Incidental_Discovery (1 variants)
  • Fabry_disease (1 variants)
  • Movement_disorder (1 variants)
  • Abnormal_brain_morphology (1 variants)
  • Abnormality_of_the_nervous_system (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GALC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000153.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
7
clinvar
311
clinvar
3
clinvar
 322
missense
21
clinvar
121
clinvar
294
clinvar
16
clinvar
3
clinvar
 455
nonsense
37
clinvar
35
clinvar
 72
start loss
4
1
 5
frameshift
80
clinvar
43
clinvar
1
clinvar
 124
splice donor/acceptor (+/-2bp)
14
clinvar
42
clinvar
 56
Total 152 246 303 327 6

Highest pathogenic variant AF is 0.0037812707

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
GALCprotein_codingprotein_codingENST00000261304 17155846
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
5.21e-150.76212468501131247980.000453
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.1863653750.9730.00001934447
Missense in Polyphen124149.030.832041770
Synonymous-0.06981361351.010.000007151286
Loss of Function1.882942.20.6870.00000216461

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0007820.000781
Ashkenazi Jewish0.0002990.000298
East Asian0.0002780.000278
Finnish0.0004670.000464
European (Non-Finnish)0.0004970.000494
Middle Eastern0.0002780.000278
South Asian0.0004590.000458
Other0.0004970.000495

dbNSFP

Source: dbNSFP

Function
FUNCTION: Hydrolyzes the galactose ester bonds of galactosylceramide, galactosylsphingosine, lactosylceramide, and monogalactosyldiglyceride. Enzyme with very low activity responsible for the lysosomal catabolism of galactosylceramide, a major lipid in myelin, kidney and epithelial cells of small intestine and colon. {ECO:0000269|PubMed:8281145, ECO:0000269|PubMed:8399327}.;
Disease
DISEASE: Leukodystrophy, globoid cell (GLD) [MIM:245200]: An autosomal recessive disorder characterized by insufficient catabolism of several galactolipids that are important for normal myelin production. Four clinical forms are recognized. The infantile form accounts for 90% of cases. It manifests before six months of age with irritability, spasticity, arrest of motor and mental development, and bouts of temperature elevation without infection. This is followed by myoclonic jerks of arms and legs, oposthotonus, hypertonic fits, and mental regression, which progresses to a severe decerebrate condition with no voluntary movements and death from respiratory infections or cerebral hyperpyrexia before 2 years of age. Cases with later onset present with unexplained blindness, weakness and sensorimotor peripheral neuropathy, mental deterioration and death. {ECO:0000269|PubMed:10234611, ECO:0000269|PubMed:10477434, ECO:0000269|PubMed:17579360, ECO:0000269|PubMed:20886637, ECO:0000269|PubMed:23462331, ECO:0000269|PubMed:8595408, ECO:0000269|PubMed:8786069, ECO:0000269|PubMed:8940268, ECO:0000269|PubMed:9272171}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Lysosome - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;Glycosphingolipid metabolism;Sphingolipid metabolism (Consensus)

Recessive Scores

pRec
0.449

Intolerance Scores

loftool
0.252
rvis_EVS
0.85
rvis_percentile_EVS
88.48

Haploinsufficiency Scores

pHI
0.0687
hipred
N
hipred_score
0.474
ghis
0.434

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.407

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Galc
Phenotype
growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; renal/urinary system phenotype;

Gene ontology

Biological process
galactosylceramide catabolic process;glycosphingolipid metabolic process;myelination
Cellular component
lysosome;lysosomal lumen
Molecular function
galactosylceramidase activity